Small particle aerosol is defined as a colloid system in which the continuous phase is a gas, and the majority of particles are less than 5 microns in diameter with an aerodynamic mass median diameter ranging from 1 to 3 microns. The advantage of such a discretely sized population of particles is that, because of their small size and low settling velocities, they will penetrate when inhaled into the lower respiratory tract in substantial percentages. For example, 1.5 micron particles will deposit 46 percent of the total inhaled dose in the lung and another 36 percent in nose and upper air passages. Such uniform deposition will permit treatment of lesions at any level of the respiratory tract (Gilbert, B. E., Wilson, S. Z., and Knight, V., 1986, Ribavirin Aerosol Treatment of Influenza Virus Infections. In: Options for the Control of Influenza. UCLA Symposium on Molecular and Cellular Biology. Alan R. Liss, Inc., New York, N.Y., p. 343.)
Small particle aerosol treatment delivers a high dose of drug to the epithelium of the respiratory tract in amounts largely unachievable by other routes of administration (Knight, V. 1973, Airborne Transmission and Pulmonary Deposition of Respiratory Viruses. In: Viral and Mycoplasmal Infections of the Respiratory Tract. V. Knight, ed. Lea and Febiger, Philadelphia, Pa., p. 1). There is a subsequent steady rate of absorption of drug into the systemic circulation.
Dried phospholipids placed into an aqueous environment will spontaneously associate into multilamellar structures that function as permeability barriers. These lipid vesicles, termed liposomes, are composed of aqueous compartments separated from each other and the external medium by a series of closed concentric lipid bilayers. The composition of the aqueous compartments is the same as the medium in which the liposomes were formed; this makes it possible to entrap a wide variety of materials within the lipid bilayers. Entrapped markers can be released by a variety of lytic agents in a manner analogous to natural membranes. Since liposomes may be prepared from substances found in normal cell membranes, they are perceived as nontoxic to mammalian host; and studies in humans and laboratory animals have supported this concept.
The ability to encapsulate water soluble compounds in liposomes led to speculation that they might be useful clinically as carriers of drugs. This expectation has not been fully realized for water soluble drugs. However, recent studies with water insoluble anticancer and antimicrobial compounds have suggested that liposomes may be ideally suited for delivery of this type of drug. The amounts of drug associated with liposomes are high and release does not occur until the membranes are destroyed either by mechanical means of biodegradation, thus allowing a more controlled release of the drug over time. Moreover, in laboratory animals the use of liposomes actually reduced toxic effects observed with the drug alone.
Liposome-drug compounds are heterogeneous in size ranging from less than 1 micron up to 10 microns in diameter and have been given in relatively large oral or intravenous doses.